chr7-101163271-C-T

Position:

• chr7-101163271-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003378.4(VGF):​c.1573G>A​(p.Glu525Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VGF NM_003378.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

Genes affected

VGF (HGNC:12684): (VGF nerve growth factor inducible) This gene is specifically expressed in a subpopulation of neuroendocrine cells, and is upregulated by nerve growth factor. The structural organization of this gene is similar to that of the rat gene, and both the translated and the untranslated regions show a high degree of sequence similarity to the rat gene. The encoded secretory protein also shares similarities with the secretogranin/chromogranin family, however, its exact function is not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2826392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGF	NM_003378.4	c.1573G>A	p.Glu525Lys	missense_variant	2/2	ENST00000249330.3
VGF	XM_005250561.6	c.1573G>A	p.Glu525Lys	missense_variant	2/2
VGF	XM_011516549.4	c.1573G>A	p.Glu525Lys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGF	ENST00000249330.3	c.1573G>A	p.Glu525Lys	missense_variant	2/2	1	NM_003378.4	P1
VGF	ENST00000445482.2	c.1573G>A	p.Glu525Lys	missense_variant	2/2	5		P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1358558 Hom.: 0 Cov.: 33 AF XY: 0.00000150 AC XY: 1 AN XY: 668168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000141

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.37e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	.;T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.65	N;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.20	T;T
Polyphen		1.0	D;D
Vest4		0.38
MutPred		0.21		Gain of methylation at E525 (P = 0.0017);Gain of methylation at E525 (P = 0.0017);
MVP		0.068
MPC		0.75
ClinPred		0.55	D
GERP RS		4.6
Varity_R		0.33
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35400704; hg19: chr7-100806552; COSMIC: COSV99973099; COSMIC: COSV99973099;